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Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells.

Leandersson, Karin LU ; Riesbeck, Kristian LU and Andersson, Tommy LU (2006) In Nucleic Acids Research 34(14). p.3988-3999
Abstract
Wnt-5a is a non-transforming Wnt protein. Since Wnt-5a mRNA and protein levels differ within and between tumours, the potential of Wnt-5a as a prognostic factor has been debated. We have previously shown that the lack of Wnt-5a protein is a predictor of shorter disease-free survival in human breast cancer. Recently, however, we also showed that the breast tumours lacking Wnt-5a protein had a high or normal level of Wnt-5a mRNA that might explain the discrepancies in previous studies. We here report that Wnt-5a is regulated at the post-transcriptional level. The regulation was mediated by the Embryonic Lethal Abnormal Vision (ELAV)like protein HuR, which inhibited translation of Wnt-5a when bound to highly conserved AU-rich sequences in the... (More)
Wnt-5a is a non-transforming Wnt protein. Since Wnt-5a mRNA and protein levels differ within and between tumours, the potential of Wnt-5a as a prognostic factor has been debated. We have previously shown that the lack of Wnt-5a protein is a predictor of shorter disease-free survival in human breast cancer. Recently, however, we also showed that the breast tumours lacking Wnt-5a protein had a high or normal level of Wnt-5a mRNA that might explain the discrepancies in previous studies. We here report that Wnt-5a is regulated at the post-transcriptional level. The regulation was mediated by the Embryonic Lethal Abnormal Vision (ELAV)like protein HuR, which inhibited translation of Wnt-5a when bound to highly conserved AU-rich sequences in the 3'-untranslated region (3'-UTR) of the Wnt-5a mRNA molecule, as shown by both HA-tagged Wnt-5a- and Luciferase-Wnt-5a-3'-UTR reporter assays. The HuR-dependent inhibition of Wnt-5a was supported by the fact that active HuR is located in the cytoplasm in invasive human breast tumours and that hypoxia-induced activation of HuR inhibits translation of both Luciferase-Wnt5a-3'-UTR and endogenous Wnt-5a protein. We propose that the lack of Wnt-5a protein expression in invasive human breast tumours is caused by a HuR-mediated suppression of Wnt-5a mRNA translation.. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nucleic Acids Research
volume
34
issue
14
pages
3988 - 3999
publisher
Oxford University Press
external identifiers
  • pmid:16914445
  • wos:000240583800020
  • scopus:33748575589
ISSN
1362-4962
DOI
10.1093/nar/gkl571
language
English
LU publication?
yes
id
5b729559-2c22-4c4d-9077-699a3da2a886 (old id 160073)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16914445&dopt=Abstract
date added to LUP
2007-07-25 15:39:07
date last changed
2018-05-29 11:13:56
@article{5b729559-2c22-4c4d-9077-699a3da2a886,
  abstract     = {Wnt-5a is a non-transforming Wnt protein. Since Wnt-5a mRNA and protein levels differ within and between tumours, the potential of Wnt-5a as a prognostic factor has been debated. We have previously shown that the lack of Wnt-5a protein is a predictor of shorter disease-free survival in human breast cancer. Recently, however, we also showed that the breast tumours lacking Wnt-5a protein had a high or normal level of Wnt-5a mRNA that might explain the discrepancies in previous studies. We here report that Wnt-5a is regulated at the post-transcriptional level. The regulation was mediated by the Embryonic Lethal Abnormal Vision (ELAV)like protein HuR, which inhibited translation of Wnt-5a when bound to highly conserved AU-rich sequences in the 3'-untranslated region (3'-UTR) of the Wnt-5a mRNA molecule, as shown by both HA-tagged Wnt-5a- and Luciferase-Wnt-5a-3'-UTR reporter assays. The HuR-dependent inhibition of Wnt-5a was supported by the fact that active HuR is located in the cytoplasm in invasive human breast tumours and that hypoxia-induced activation of HuR inhibits translation of both Luciferase-Wnt5a-3'-UTR and endogenous Wnt-5a protein. We propose that the lack of Wnt-5a protein expression in invasive human breast tumours is caused by a HuR-mediated suppression of Wnt-5a mRNA translation..},
  author       = {Leandersson, Karin and Riesbeck, Kristian and Andersson, Tommy},
  issn         = {1362-4962},
  language     = {eng},
  number       = {14},
  pages        = {3988--3999},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells.},
  url          = {http://dx.doi.org/10.1093/nar/gkl571},
  volume       = {34},
  year         = {2006},
}